ESPE Abstracts

Background: Congenital adrenal insufficiency represents a life-threatening condition. Among its multiples causes, mutation of NNT1 is the most recently discovered. We had the opportunity to observe one case. NNT1 is a gene coding for a membrane protein which protects cells from oxidative stress.

Objective and hypotheses: As few cases have been published until now, we describe a new case.

Results: In a consanguineous (second grade) Algerian family, a first-born female child deceased at the age of 4 years, in the context of urinary infection. A second female child presented in Algeria melanodermia detected at the age of 8 months. At this time, plasma ACTH at 500 pg/ml and undetectable aldosterone levels indicated global adrenal insufficiency. She was then treated with 20 mg/m² per day hydrocortisone only. Melanodermia disappeared under treatment. However, ACTH levels remained incompletely corrected at 1 year of age. When she was 8 years old, during holidays in France, she suffered from asthenia, muscular weakness, bone pains and anorexia, without melanodermia. External genitalia were normal. Biologically, cortisol was undetectable, all intermediate plasma adrenal steroid compounds undetectable too, 17 hydroxyprogesterone included. ACTH was 356 pg/ml. Renin plasma activity was moderately increased (56 ng/ml per h) witnessing a residual moderate mineralocorticoid deficiency. SRY sequencing was negative. All known causes of adrenal global deficiency were eliminated. Exon sequencing of NNT 1 gene revealed a p.Met337Val or c.1009A>G homozygous mutation in exon 9. This mutation corresponded to the NADH binding domain of the protein (Pr Y Morel, Lyon). Extension investigations (growth, liver functions, cardiac ultrasound, skeletal X rays) were normal. Then hydrocortisone and fludrocortisone doses were adjusted.

Method: Case report.

Conclusion: Intrafamilial severity of NNT1 mutation may be variable. Mutations determining other functions of the gene have also been described. Following up extension investigations, especially cardiac, is mandatory.